2-201381221-TAAAAA-TAAAA

Variant names:

• chr2-201381221-TA-T
• rs3832088
• NM_015049.3:c.2070-4delT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015049.3(TRAK2):​c.2070-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.033 (1 hom.)
• Consequence: TRAK2 NM_015049.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 4 publications found

Genes affected

TRAK2 (HGNC:13206): (trafficking kinesin protein 2) Predicted to enable GABA receptor binding activity and myosin binding activity. Predicted to be involved in several processes, including mitochondrion distribution; organelle transport along microtubule; and protein targeting. Predicted to be located in cytoplasm and plasma membrane. Predicted to be active in cytoplasmic vesicle; dendrite; and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015049.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK2	NM_015049.3	MANE Select	c.2070-4delT		splice_region intron	N/A	NP_055864.2	O60296-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAK2	ENST00000332624.8	TSL:1 MANE Select	c.2070-4delT		splice_region intron	N/A	ENSP00000328875.3	O60296-1
	TRAK2	ENST00000861749.1		c.2139-4delT		splice_region intron	N/A	ENSP00000531808.1
	TRAK2	ENST00000861746.1		c.2070-4delT		splice_region intron	N/A	ENSP00000531805.1

Frequencies

GnomAD3 genomes AF: 0.00146 AC: 212 AN: 144788 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00348

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000893

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000425

Gnomad FIN AF: 0.00184

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000631

Gnomad OTH AF: 0.00251

GnomAD2 exomes AF: 0.0356 AC: 6295 AN: 176994 AF XY: 0.0334

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0446

Gnomad ASJ exome AF: 0.0344

Gnomad EAS exome AF: 0.0584

Gnomad FIN exome AF: 0.0260

Gnomad NFE exome AF: 0.0270

Gnomad OTH exome AF: 0.0325

GnomAD4 exome AF: 0.0327 AC: 43860 AN: 1342578 Hom.: 1 Cov.: 0 AF XY: 0.0322 AC XY: 21290 AN XY: 662140

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.118 AC: 3217 AN: 27166

American (AMR) AF: 0.0498 AC: 1489 AN: 29924

Ashkenazi Jewish (ASJ) AF: 0.0384 AC: 851 AN: 22140

East Asian (EAS) AF: 0.0927 AC: 3284 AN: 35416

South Asian (SAS) AF: 0.0239 AC: 1772 AN: 74286

European-Finnish (FIN) AF: 0.0301 AC: 1474 AN: 49026

Middle Eastern (MID) AF: 0.0530 AC: 269 AN: 5078

European-Non Finnish (NFE) AF: 0.0282 AC: 29439 AN: 1044742

Other (OTH) AF: 0.0377 AC: 2065 AN: 54800

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00152 AC: 220 AN: 144834 Hom.: 0 Cov.: 0 AF XY: 0.00160 AC XY: 113 AN XY: 70488

African (AFR) AF: 0.00360 AC: 136 AN: 37746

American (AMR) AF: 0.000960 AC: 14 AN: 14576

Ashkenazi Jewish (ASJ) AF: 0.000293 AC: 1 AN: 3408

East Asian (EAS) AF: 0.00 AC: 0 AN: 4892

South Asian (SAS) AF: 0.000426 AC: 2 AN: 4700

European-Finnish (FIN) AF: 0.00184 AC: 18 AN: 9808

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.000631 AC: 42 AN: 66546

Other (OTH) AF: 0.00348 AC: 7 AN: 2014

Alfa AF: 0.000759 Hom.: 1046

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.18
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3832088; hg19: chr2-202245944; COSMIC: COSV60272046;